Is there a role for surgery after chemotherapy in recurrent/metastatic adrenal cortical cancer (ACC)?
Authors: Esmail Mutahar Al-Ezzi, Abhenil Mittal, Olubukola Ayodele, Lama Amer, Xuan Li, Daniel Vilarim Araujo, Eoghan Ruadh Malone, Shereen Ezzat, Jesse Pasternak, Ozgur Mete, Vikaash Kumar, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2022)

5092 Background: ACC is a rare endocrine malignancy. Patients with metastatic disease at diagnosis are often treated palliatively with systemic therapy. It is unclear if neoadjuvant cytoreduction with chemotherapy can render metastatic or previously resected but locally recurrent patients become surgical candidates and impact overall survival (OS). Methods: A retrospective single institution review (2002-2019) of metastatic ACC patients was performed. Descriptive statistics were used and OS was estimated by Kaplan-Meier method. Results: Out of 84 patients with metastatic ACC [30 (20.7%) upfront and 54 (37.2%) after definitive therapy], 51 received systemic therapy with mitotane and etoposide-doxorubicin-cisplatin (EDP) as standard 1 st line regimen and varied subsequent lines of therapy. Two patients were excluded as they were lost to follow-up. Among the included 49 patients, 29 were females (59.2%) and 26 patients (53.1%) had functional tumors at baseline. Out of 33 patients who had information available on tumor grade, 26 (78.8%) were high grade. Nine pts (18.4%) underwent surgery after receiving systemic therapy (eight after EDP in first line and one after pembrolizumab in third line). These patients were younger (median age 39 years compared to 52.5 years for those receiving only chemotherapy), had locally recurrent disease (all nine patients) with four having evidence of progressive liver metastasis. Median number of EDP cycles delivered before surgery was 4 (range 3-7). The patient who underwent surgery after pembrolizumab received nine cycles of preoperative pembrolizumab. Five pts (55.5%) had partial response, three (33.3%) had disease progression and one (11.1%) had stable disease prior to surgery. Patients underwent surgery after a mean interval of 3.1 months (m) (1.1-5.1) after systemic therapy. Six patients had no evidence of disease (NED) (five with disease limited to adrenal bed) after surgery. Eight out of nine patients recurred after surgery with a median time of 6.1 m (4.4-7.8). The median OS for the entire cohort was 26 m (95% CI 22.3-35.2). This was not significantly better for patients undergoing surgery [median OS 31.2 m (95% CI 21.4-63.3) vs 24.7 m (95% CI 17.7-35.2) p = 0.48]. Patients rendered NED after surgery had numerically better OS than those with residual disease or those receiving only chemotherapy [median OS 39.6 m (24.8.-NR), vs 23.5 m (21.4-NR) vs 24.7 m (17.7-35.2), p = 0.271]. Higher Ki-67 predicted for inferior OS in the entire cohort with no effect of age, gender, tumor grade or functional status. Conclusions: Attempting to downstage patients with metastatic or locally recurrence with systemic therapy does not seem to prolong OS in patients with ACC. Selected patients with limited disease burden, who can be rendered disease free by surgery, may be suitable for this approach.